The emphasis of our research is placed upon investigating probable cellular components or processes involved in hyperthermic cell damage. One probable cellular target is the plasma membrane, composed primarily of cholesterol, fatty acids, phospholipids and membrane proteins. Hyperthermia, as well as changes in these selected components, independently effect the permeability and the structure integrity of a cell. Extensive analysis and modification of these components is a major objective of this work and will utilize cells grown in culture and tissue from animal and human tumors. The second major objective is to define the extent to which the polyamines are involved in modifying or determining a cellular thermal response. This will be achieved by studying the effects of heat on ornithine decarboxylase (ODC), the ODC antizyme, S-adenosyl-L-methionine decarboxylase (SAMDC) and the direct measurement of the concentrations and metabolism of the polyamines. In addition, an exogenous supplement of polyamines appears to enhance thermal sensitivity. The third major objective is to analyze further the role of nutrients, growth factors and cellular byproducts (which result when cells are heated) in either the protection or enhanced killing of cells by heat. Cells grown in culture, principally in defined media, will be exploited.